Enhancement of peritoneal leukocyte function by granulocyte colony-stimulating factor in rats with abdominal sepsis.
OBJECTIVE
To investigate the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and peritoneal neutrophils during intra-abdominal sepsis.


METHODS
Placebo, controlled study, using a rat model of intra-abdominal sepsis.


METHODS
Animal research facility.


METHODS
Male specific pathogen-free Sprague-Dawley rats.


METHODS
Abdominal sepsis was produced in rats by cecal ligation and puncture. The control animals received a sham operation. G-CSF (subcutaneous injection at 50 microg/kg) or vehicle (100 microL of 5% dextrose) treatment was initiated at 1 hr after cecal ligation and puncture or sham operation and repeated at 12-hr intervals thereafter.


RESULTS
Six hours after cecal ligation and puncture, CD11b/c and CD18 expression on circulating neutrophils was significantly up-regulated when compared with those in the sham operated control animals. Peritoneal neutrophils exhibited a further up-regulation of these adhesion molecules than did the circulating neutrophils. A sustained up-regulation of CD11b/c and CD18 was found in peritoneal neutrophils even at 24 hrs after cecal ligation and puncture. G-CSF treatment increased CD11b/c expression on circulating neutrophils in 6-hr sham-operated rats, but did not further up-regulate CD11b/c or CD18 expression on circulating or peritoneal neutrophils in cecal ligation and puncture rats. Phagocytic activities of circulating neutrophils assessed by uptake of fluorescent latex microspheres were lower in 24-hr cecal ligation and puncture rats when compared with the sham-operated controls. G-CSF treatment prevented this inhibition. Furthermore, G-CSF enhanced the phagocytic activities of peritoneal neutrophils in both 6- and 24-hr cecal ligation and puncture rats when compared with those of the vehicle-treated animals. Spontaneous hydrogen peroxide generation by circulating neutrophils was increased in 6-hr cecal ligation and puncture rats, but not in 24-hr cecal ligation and puncture rats. Peritoneal neutrophils exhibited an inhibition of phorbol myristate acetate-stimulated hydrogen peroxide generation. G-CSF treatment did not up-regulate neutrophil hydrogen peroxide generation.


CONCLUSIONS
Circulating and peritoneal neutrophils exhibit marked polymorphism in their functional activities during the host response to abdominal sepsis. G-CSF treatment significantly enhanced the phagocytic function of both circulating and peritoneal neutrophils which may be one mechanism underlying its protective effect in abdominal sepsis.
Zhang
P
P
Department of Medicine, Louisiana State University Medical Center, New Orleans, USA.
Bagby
G J
GJ
Stoltz
D A
DA
Summer
W R
WR
Nelson
S
S
D000005:Abdomen; D000818:Animals; D018821:CD18 Antigens / Q000032:analysis / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016167:Integrin alphaXbeta2 / Q000032:analysis / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology*; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D018821:CD18 Antigens; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor